In time-of-flight mass spectrometers (TOFMS), a sample to be analyzed is ionized, the resulting ions are accelerated in a vacuum by an electrical pulse having a known potential, and the time of flight of the ions of different masses to an ion detector are measured. The more massive the ion, the longer is the time of flight. The relationship between the time of flight and the mass, m, of ions of a given mass can be written in the form:time=k√{square root over (m)}+c where k is a constant related to flight path and ion energy, and c is a small delay time that may be introduced by the signal cable and/or detection electronics. When the term mass is used in this disclosure in the context of mass spectrometry, it is to be understood to mean mass-to-charge ratio. The process of accelerating the ions of the sample and detecting the arrival times of the ions of different masses at the ion detector will be referred to herein as a mass scan operation.
The ion detector generates electrons in response to ions incident thereon. The electrons constitute an electrical signal whose amplitude is proportional to the number of electrons. There is only a statistical correlation between the number of electrons generated in response to a single ion incident on the ion detector. In addition, more than one ion at a time may be incident on the ion detector due to ion abundance.
In the mass spectrometer, an ion pulser generates a short burst of ions by applying what is referred to in the art as a transient to ions received from an ion source. A transient is a short-duration electrical pulse having a known voltage. Immediately after leaving the ion pulser, the ions are bunched together but, within the ion burst, ions of different masses travel at different speeds. The time of flight required for the ions of a given mass to reach the ion detector depends on the speed of the ions, which in turn, depends on the mass of the ions. Consequently, as the ion burst approaches the ion detector, the ion burst is separated in space and in time into discrete packets, each packet containing ions of a single mass. The packets reach the ion detector at different arrival times that depend on the mass of the ions therein.
The mass spectrometer generates what will be referred to as a mass scan signal in response to a single burst of ions accelerated by the ion pulser in response to a single transient. The mass scan signal is a digital signal that represents the output of the ion detector as a function of time. The time represents the time of flight of the ions from the ion pulser to the ion detector. The number of electrons generated by the ion detector in a given time interval constitutes an analog ion detection signal that is converted to the mass scan signal by an analog-to-digital converter (A/D converter). The mass scan signal represents the output of the ion detector as a function of the flight time taken by the ions to reach the ion detector. The mass scan signal is a temporal sequence of digital samples output by the A/D converter after the ions have been accelerated. The conversion time of the A/D converter effectively divides the time axis into discrete segments and the A/D converter outputs a single digital sample for each temporal segment.
Because the relationship between the amplitude of the ion detection signal output by the ion detector and the number of ions incident on the ion detector during the temporal segment is a statistical one, a single mass scan signal will not accurately represent the time-of-flight spectrum of the sample. In addition, the ion detection process is subject to noise from a number of different noise sources. Such noise causes the ion detector to generate an output signal even in the absence of ions incident on the ion detector. To overcome these problems, the mass spectrometer generates multiple mass scan signals and sums the most-recently generated mass scan signal with an accumulation of previously-generated mass scan signals to generate a time-of-flight spectrum having a defined statistical accuracy and signal-to-noise ratio. The time-of-flight spectrum is a set of data that represents the relationship between the accumulated ion intensities and time of flight. A mass spectrum is then obtained by subjecting the time-of-flight spectrum to processing such as that described in U.S. Pat. No. 7,412,334 of Fjeldsted et al., or in U.S. patent application Ser. No. 12/242,110 of Hidalgo et al., both assigned to the assignee of this disclosure.
In a conventional mass spectrometer, the ion pulser fires at a constant repetition rate chosen such that the minimum time that elapses between ion pulser firings is greater than the maximum time of flight of the mass spectrometer. This repetition rate will be referred to herein as a reference repetition rate. The maximum time of flight is typically the time of flight of the most massive ion species that the mass spectrometer is specified to measure. However, in embodiments in which the repetition rate can be adjusted, the maximum time of flight is the time of flight of the most massive ion species in the analyte. A repetition rate chosen as just described prevents a given mass scan signal from representing the times of flights of ions accelerated by different firings of the ion pulser, a phenomenon that will be referred to herein as aliasing.
A high mass resolution, a high sensitivity and a high productivity are desirable properties of a mass spectrometer. Increasing the distance between the ion pulser and the ion detector increases the mass resolution of the mass spectrometer, but undesirably increases the minimum time between consecutive firings of the ion pulser. A high sensitivity allows low-abundance ion species to be reliably detected. Increasing the number of mass scans contributing to each time-of-flight spectrum increases the sensitivity of the mass spectrometer but undesirably increases the acquisition time, i.e., the time needed to acquire each time-of-flight spectrum. Thus, in conventional mass spectrometers, mass resolution and sensitivity can be obtained only at the expense of decreased productivity.
Productivity-increasing techniques employing randomized firings of the ion pulser at an average repetition rate greater than the reference repetition rate together with active or passive de-aliasing have been known for many years. For example, U.S. Pat. No. 5,396,065 of Myerholtz et al, assigned to the assignee of this disclosure, discloses a mass spectrometer in which the minimum interval between consecutive firings of the ion pulser is less than that corresponding to the reference repetition rate. The ion pulser has a fixed repetition rate, but a random distribution is used to decide whether to fire the pulser or not. A de-aliasing technique employing a correlator is used to derive a time-of-flight spectrum from the detection signal produced by the ion detector. None of the known productivity-increasing techniques is currently in widespread use possibly because the increase in productivity is obtained at the expense of one or more of decreased accuracy, decreased sensitivity, decreased mass resolution and increased complexity.
Accordingly, what is needed is a mass spectrometer in which increased productivity is obtained without decreasing accuracy, sensitivity and mass resolution and with an acceptable increase in complexity.